R-脊椎蛋白1表达与Wnt/β-catenin信号通路在乳腺癌中的相关性及临床意义

Expression and its clinical significance of RSPO1 and Wnt/β-cateninin signaling pathway in breast invasive carcinoma

目的探讨R-脊椎蛋白1(RSPO1)、Wnt/β-catenin与乳腺癌生物学行为的相关性及其可能的机制。方法收集惠州市中心人民医院2009年1月至2015年12月乳腺癌病例标本,采用组织芯片免疫组织化学SP法,检测224例非特殊型乳腺浸润性癌(BIC-NST)、155例乳腺导管原位癌(BDCIS)及379例癌旁正常组织(NBTAC)中RSPO1、SFRP1、β-catenin的表达。结果RSPO1和β-catenin在BIC-NST及BDCIS组织中的表达明显高于NBTAC(P<0.01),而SFRP1在BIC-NST及BDCIS组织中的表达明显低于NBTAC(P<0.01);RSPO1和β-catenin在高级别BDCIS的表达率明显高于低级别组(P<0.01),在Ⅲ级BIC-NST分化组的表达率明显高于Ⅰ级分化组,而且组织分级越高RSPO1和β-catenin的表达越高,两者之间呈明显的正相关(r=0.114,P=0.023);但SFRP1在Ⅲ级BIC-NST分化组的表达率明显低于Ⅰ级分化组,且组织分级越高其表达越低,与RSPO1和β-catenin的表达均呈明显的负相关(r=-0.217,P=0.011)。RSPO1和β-catenin表达在患者临床分期Ⅲ+Ⅳ期中的表达明显高于Ⅰ+Ⅱ期的表达,且与淋巴结转移、脉管浸润相关(P<0.01);而SFRP1的表达有相反结果。结论RSPO1、β-catenin蛋白的高表达和SFRP1蛋白的低表达与乳腺癌的发生、发展密切相关,可为乳腺癌的诊断和靶向治疗提供新的靶点。

Objective To investigate the role of RSPO1 and Wnt/β-catenin signaling pathway in the biological behavior of breast cancer and the underlying mechanisms.Methods Breast cancer specimens were collected from January 2009 to December 2015 in Huizhou Municipal Center People Hospital.The expression of RSPO1,SFRP1 andβ-catenin of 224 cases with breast invasive carcinoma of no specific type(BIC-NST),155 cases with breast ductal carcinoma in situ(BDCIS)and 379 cases with normal breast tissues adjacent to carcinoma(NBTAC)were detected by tissue-microarray and SP immunohistochemical staining.Results Expression of RSPO1 andβ-catenin in BIC-NST and BDCIS were significantly higher than those in NBTAC(P<0.01),whereas the expression of SFRP1 in BIC-NST and BDCIS was apparently lower than that in NBTAC(P<0.01).Expression of RSPO1 andβ-catenin in gradeⅢBIC-NST group and high-grade BDCIS group were significantly higher than that in the grade I BIC-NST group and low-grade BDCIS group.There was a positive correlation between histological grade and the expression of RSPO1 andβ-catenin(P<0.05).Moreover,expression of RSPO1 positively correlates withβ-catenin levels in BICNST specimens(r=0.114,P=0.023).However,the expression of SFRP1 in gradeⅢBIC-NST group was apparently lower than that in gradeⅠgroup,and there was a significantly negative correlation between SFRP1 and histological grade(P<0.01),as well as with levels of RSPO1 andβ-catenin(r=-0.217,P=0.011).Furthermore,expression of RSPO1 andβ-catenin in clinical stagesⅢ+ⅣBIC-NST were significantly higher than that in stagesⅠ+Ⅱ(P<0.01).Meanwhile,expression levels of RSPO1 andβ-catenin were significantly associated with lymph node metastasis and vascular invasion(P<0.01).However,expression of SFRP1 showed the opposite results.Conclusion High expression of RSPO1 andβ-catenin,and low expression of SFRP1 were closely related to the recurrence and development of breast carcinoma,which could provide a new target for diagnosis and treatment of breast carcinoma.